Current understanding of human genetics and genetic analysis of psoriasis
Authors:
Open Access
- 21 February 2012
- journal article
- review article
- Published by Wiley in The Journal of Dermatology
- Vol. 39 (3) , 231-241
Abstract
During the past 5 years, genome‐wide association studies (GWAS), primarily based on single nucleotide polymorphism markers, have identified many loci as potential psoriasis susceptibility regions. These studies appeared to provide strong evidence because the susceptibility genes are involved in the interleukin‐23/T‐helper 17 axis of psoriasis immunopathogenesis and/or skin barrier functions. However, the “identified” genes only explained a small proportion of psoriasis heritability, although it is known to be comparatively higher than that of other common diseases. GWAS are based on the hypothesis that disease‐causing variants are high frequency variants within populations. However, this hypothesis is problematic because deleterious variants such as those predisposing to specific diseases will generally not be maintained by selection pressure throughout human evolution. This issue also affects psoriasis studies. Here, we review the current paradigm shift in human genetic analyses and its implications for detection of psoriasis‐causing variants based on linkage analysis and GWAS, except the well‐known psoriasis susceptibility locus HLA‐C.Keywords
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